Background
erenumab was safe and effective in clinical trials for the prevention of migraine. However, real-life data are still lacking. Here we report the clinical experience from an Italian ...real-world setting using erenumab in patients with chronic migraine experiencing previous unsuccessful preventive treatments.
Methods
Seventy patients with chronic migraine and failure to ≥4 migraine preventive medication classes initially received monthly erenumab 70 mg s.c. Patients without a clinically meaningful improvement, considered as a > 30% reduction in headache days per month, after ≥3 months of therapy switched to monthly erenumab 140 mg. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity and migraine-related disability and impact, and validated questionnaires to explore depression/anxiety, sleep, and quality of life (QoL). Finally, the Pain Catastrophizing Scale, Allodynia Symptom Checklist-12 and MIGraine attacks-Subjective COGnitive impairments scale (MIG-SCOG) were administered.
Results
70% of patients were “responders” after the third administration of erenumab 70 mg, whereas 30% switched to erenumab 140 mg; 29% (6 pts) responded after the sixth administration. The headache-day frequency was reduced from 21.1 ± 0.7 to 11.4 ± 0.9 days after the third administration (
p
< 0.001) and to 8.9 ± 0.7 days after the sixth administration (
p
< 0.001). 53% and 70% of patients, respectively, showed a reduction of ≥50% of headache days/month after the third and the sixth administrations.
Also improved were headache pain severity, migraine-related disability, and impact on daily living, QoL, pain catastrophizing and allodynia (all
p
< 0.001), quality of sleep, symptoms of depression or anxiety (
p
< 0.05) but not MIG-SCOG. There were no new adverse event signals.
Conclusion
These real-world data support monthly erenumab 70 or 140 mg s.c. as a safe and effective preventive treatment to reduce headache frequency and severity in chronic migraine patients experiencing previous unsuccessful preventive treatments.
Objectives:
To investigate resting-state functional connectivity (RS-FC) of the default-mode network (DMN) and of sensorimotor network (SMN) network in relapsing remitting (RR) multiple sclerosis ...(MS) patients with fatigue (F) and without fatigue(NF).
Methods:
In all, 59 RRMS patients and 29 healthy controls (HC) underwent magnetic resonance imaging (MRI) protocol including resting-state fMRI (RS-fMRI). Functional connectivity of the DMN and SMN was evaluated by independent component analysis (ICA). A linear regression analysis was performed to explore whether fatigue was mainly driven by changes observed in the DMN or in the SMN. Regional gray matter atrophy was assessed by voxel-based morphometry (VBM).
Results:
Compared to HC, F-MS patients showed a stronger RS-FC in the posterior cingulate cortex (PCC) and a reduced RS-FC in the anterior cingulated cortex (ACC) of the DMN. F-MS patients, compared to NF-MS patients, revealed (1) an increased RS-FC in the PCC and a reduced RS-FC in the ACC of the DMN and (2) an increased RS-FC in the primary motor cortex and in the supplementary motor cortex of the SMN. The regression analysis suggested that fatigue is mainly driven by RS-FC changes of the DMN.
Conclusions:
Fatigue in RRMS is mainly associated to a functional rearrangement of non-motor RS networks.
Background
Anxiety, depression and reduction of quality of life (QoL) are common in people with multiple sclerosis (pwMS). Fear of getting sick from COVID-19, government’s lockdown and the imposed ...social distancing might have had an impact on psychological distress and QoL.
Objectives
The aim of our study was to investigate anxiety, depression and QoL changes in pwMS during SARS-CoV-2 outbreak and lockdown in Italy.
Methods
67 pwMS with a previous (less than 6 months) neuropsychological evaluation before SARS-CoV-2 outbreak (T0) were re-evaluated at the time of the outbreak and lockdown in Italy (T1). They underwent a clinical and neurological evaluation and completed the State-Trait Anxiety Inventory (STAI-Y1), the Beck Depression Inventory second edition (BDI-II), and Multiple Sclerosis Quality of Life-54 (MsQoL-54) at T0 and T1. Benjamini–Hochberg procedure was applied to control the false discovery rate.
Results
BDI-II and STAI-Y1 scores did not change between T0 and T1. At T1, MsQoL-54 scores were higher on the satisfaction with sexual life and the social function subscales, and lower on the limitation due to emotional problems subscale.
Conclusions
This is the first study that evaluated mood and QoL levels before and during the lockdown due to COVID-19 pandemic in pwMS. No worsening of anxiety and depression levels was found. Contrariwise some improvements were noted on QoL, the most reliable regarding the sexual satisfaction and the social function.
Many patients with multiple sclerosis (MS) experience information processing speed (IPS) deficits, and the Symbol Digit Modalities Test (SDMT) has been recommended as a valid screening test. Magnetic ...resonance imaging (MRI) has markedly improved the understanding of the mechanisms associated with cognitive deficits in MS. However, which structural MRI markers are the most closely related to cognitive performance is still unclear. We used the multicenter 3T‐MRI data set of the Italian Neuroimaging Network Initiative to extract multimodal data (i.e., demographic, clinical, neuropsychological, and structural MRIs) of 540 MS patients. We aimed to assess, through machine learning techniques, the contribution of brain MRI structural volumes in the prediction of IPS deficits when combined with demographic and clinical features. We trained and tested the eXtreme Gradient Boosting (XGBoost) model following a rigorous validation scheme to obtain reliable generalization performance. We carried out a classification and a regression task based on SDMT scores feeding each model with different combinations of features. For the classification task, the model trained with thalamus, cortical gray matter, hippocampus, and lesions volumes achieved an area under the receiver operating characteristic curve of 0.74. For the regression task, the model trained with cortical gray matter and thalamus volumes, EDSS, nucleus accumbens, lesions, and putamen volumes, and age reached a mean absolute error of 0.95. In conclusion, our results confirmed that damage to cortical gray matter and relevant deep and archaic gray matter structures, such as the thalamus and hippocampus, is among the most relevant predictors of cognitive performance in MS.
We developed an advanced machine learning pipeline to identify brain structural magnetic resonance imaging (MRI) volumes that, along with demographic and clinical data, predict information processing speed (IPS) performance, assessed with the Symbol Digit Modalities Test (SDMT), of patients with multiple sclerosis (MS). In this study, we used a multicenter 3T‐MRI data set of 540 MS patients. We confirmed that damage of cortical gray matter and relevant deep and archaic gray matter structures, such as the thalamus and hippocampus, is among the most relevant predictors of cognitive performance in MS.
Background
Two‐thirds of patients with migraine without aura (MwoA) complain ictal cutaneous allodynia (CA), clinical sign of central nociceptive pathway sensitization, and independent predictor for ...migraine chronification.
Aim
We aimed to investigate whether functional abnormalities, structural, or microstructural changes of the main cognitive networks (default mode network DMN, salience network SN, and central executive network CEN) could predict the development of CA in patients with MwoA.
Methods
Baseline 3‐Tesla MRI images of 50 patients with MwoA were analyzed between 2009 and 2015. Over a three‐year period, patients were then stratified into 2 groups based on CA development and compared with matched healthy controls (HC). Group‐level independent components analysis was used to investigate intrinsic functional connectivity (FC) differences within the cognitive resting‐state networks. Voxel‐based morphometry (VBM) was used to assess whether group differences in cognitive network FC were related to structural differences. Tract‐based spatial statistical analyses (TBSS) were conducted to assess the microstructural properties of white matter tracts. We also compared internetwork connectivity between patients. Finally, a logistic regression analysis was used to investigate baseline imaging predictors of CA development.
Results and Discussion
We observed a significantly reduced FC of both DMN and CEN in patients with MwoA developing CA (MwoA dCA) when compared with both patients with MwoA not developing CA (MwoA ndCA) and HC. Within the DMN, the PCC/precuneus is a key hub aimed to anti‐nociception and multisensory integration. The reduced intrinsic PCC/precuneus FC observed in patients with MwoA dCA could subtend abnormal inputs integration, from different sensory modalities, allowing the development of CA. On the other hand, within the CEN, a central role in pain modulation as well as in executive functions is played by ACC and MFG. Our finding of reduced ACC and MFG FC in MwoA dCA may represent the neuronal substrate of both subclinical impairment of complex executive functions and dysfunctional anti‐nociceptive pathway, making these patients more prone to migraine chronification. TBSS analyses showed a statistically significant reduced corpus callosum (CC) FA in patients with MwoA dCA as previously demonstrated in migraine patients with other chronification factors such as medication overuse or affective disorders. No VBM differences in both global and local volumes were revealed between groups. No significant correlations have been found between the observed functional and microstructural changes and clinical parameters of disease severity. Logistic regression analysis indicated that the full model containing all predictors was statistically significant while the decreased ACC‐FC was significantly associated with CA development.
Conclusion
We suggest that DMN and CEN FC abnormalities as well as CC microstructural changes could represent a prognostic imaging biomarker able to identify migraine patients more prone to experiencing CA and therefore, more inclined to chronic migraine. In the new pharmacological scenario, it would be useful to address therapeutic resources to specific migraine populations with a high risk of more severe clinical phenotype.
Objectives
Several concerns regard the immunogenicity of SARS-CoV-2 vaccines in people with multiple sclerosis (pwMS), since the majority of them is treated with immunomodulating/immunosuppressive ...disease modifying therapies. Here we report the first data on the humoral response to mRNA SARS-CoV-2 vaccine in a case series of 4 pwMS treated with ocrelizumab (OCR) as compared to a group of healthy subjects (HS).
Methods
We collected serum samples at 0, 14, 21 days after the first dose and 7 days after the second dose of BNT162b2-mRNA-Covid-19 vaccine from 55 health-care workers and 4 relapsing pwMS on OCR, with no history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgGtiters were expressed in Binding Antibody Units (BAU), an international standard unit.
Results
At baseline all subjects were negative for anti-spike IgG. Seven days after the second dose of vaccine all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I. 95% 1512.7-2672) while the 4 pwMS showed a lower response (range <4.81-175 BAU/mL).
Discussion
Humoral response to BNT162b2-mRNA-vaccine in pwMS treated with OCR was clearly blunted. Further data are urgently needed to confirm and expand these preliminary results and to develop strategies to optimize the response to SARSCoV-2 vaccines in pwMS on OCR.
Background
Although migraine is recognized as one of the most common and disabling diseases in the world, it is nonetheless still underestimated, underdiagnosed, and undertreated. The fact that ...migraine patients often tend to access the Web to search for headache‐related information hinders patient‐doctor relationships and one should also bear in mind that, unfortunately, text readability and medical literacy in the overall population may be the reason why patients' understanding of health information is compromised.
Aim
We aimed to assess the readability of the home page of the top 10 patient – oriented migraine‐related websites and the educational level required to be in a position to broach them.
Methods
On April 15, 2018, we conducted a descriptive study on the international version of Google by entering the words “headache” and “migraine.” We then analyzed the overall level of readability of texts of the home pages of the top 10 patient‐oriented websites, by means of the Simple Measure of Gobbledygook Readability Calculator.
Results
Entering “headache” on the home pages of the top 10 patient‐oriented websites on Google we found that to understand these particular websites with ease, an average grade level of 12.4 (±1.5 standard deviation, SD) and an average 13.3 years of formal education (±1.7 SD) were required. Similarly, typing “migraine” on Google we found an average grade level of 10.8 (±1.2 SD) and an average of 12.5 years of formal education (±1.9 SD) were required. The most frequently viewed websites all failed to meet the USA National Institutes of Health guidelines, which recommend a range between 6th and 7th grade level readability.
Discussion
The present study shows the low readability level resulting from the top 10 patient‐oriented headache/migraine websites and the consequent barrier this creates in the dissemination of headache/migraine‐related medical information. Although the actual physicians, both primary care physicians and headache specialists are the principal source of understandable headache‐related information, only a minority of people consult these professionals. Given the foregoing, the majority of migraine patients is, therefore, unable to obtain adequate comprehensible health information on the Web. Furthermore, the existing gap between migraine‐related website content readability and the unmet need for migraine patients to obtain pertinent and correct information might well contribute to the worldwide neglect of migraine as a major public health problem.
Conclusion
Physician experts in headache and migraine should actively cooperate in planning informative material to establish what information patients need to know, how they should use it, and how readable that material actually is. Readability ought to be established before the final website publication. Plain language ought to be used and written messages should be supplemented with visual content such as simple drawings. We recommend the setting up of a new dynamic, modern, plain‐talking, and efficient approach in communication aimed at catching the public’s attention with its readability and thus satisfying a migraine and headache web scenario.
Background:
The relationship between cognitive performance and regional thalamic atrophy in multiple sclerosis (MS) has been investigated in recent studies.
Objective and methods:
To further assess ...this relationship, 118 relapsing-remitting MS patients and 52 healthy controls underwent a neuropsychological assessment and a 3T-MRI (3-Tesla magnetic resonance imaging). Cognitive performances were correlated with thalamic shape changes by using Vertex Analysis.
Results:
Information processing speed performance correlated with atrophy of frontal/motor-connected thalamic sub-regions. Inhibitory control performance correlated with atrophy of all thalamic sub-regions. Global cognitive status correlated with atrophy of frontal/temporal-connected sub-regions.
Conclusions:
These findings support the hypothesis that, within the thalamus, the damage of the anterior regions is most relevant for cognitive dysfunction.
To evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients.
Baseline 3.0T ...brain and cervical cord T2-weighted and three-dimensional T1-weighted MRI was acquired in 367 patients with MS (326 relapse-onset and 41 progressive-onset) and 179 healthy controls. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (IQR=4.8-5.2). At follow-up, patients were classified as clinically stable/worsened according to EDSS changes. Generalised linear mixed models identified predictors of clinical worsening, evolution to secondary progressive (SP) MS and reaching EDSS=3.0, 4.0 and 6.0 milestones at 5 years.
At follow-up, 120/367 (33%) patients with MS worsened clinically; 36/256 (14%) patients with relapsing-remitting evolved to SPMS. Baseline predictors of EDSS worsening were progressive-onset versus relapse-onset MS (standardised beta (β)=0.97), higher EDSS (β=0.41), higher cord lesion number (β=0.41), lower normalised cortical volume (β=-0.15) and lower cord area (β=-0.28) (C-index=0.81). Older age (β=0.86), higher EDSS (β=1.40) and cord lesion number (β=0.87) independently predicted SPMS conversion (C-index=0.91). Predictors of reaching EDSS=3.0 after 5 years were higher baseline EDSS (β=1.49), cord lesion number (β=1.02) and lower normalised cortical volume (β=-0.56) (C-index=0.88). Baseline age (β=0.30), higher EDSS (β=2.03), higher cord lesion number (β=0.66) and lower cord area (β=-0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS (β=1.87) and cord lesion number (β=0.54) predicted EDSS=6.0 (C-index=0.91).
Spinal cord damage and, to a lesser extent, cortical volume loss helped predicting worse 5-year clinical outcomes in MS.
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